Hong Huangming, Chen Zegeng, Zhang Mingzhi, Peng Zhigang, Shen Jianzhen, Shuang Yuerong, Zhou Hui, Guo Hongqiang, Huang He, Li Fei, Qian Zhengzi, Liu Lihong, Wang Liang, Yang Wei, Zhang Liling, He Pengcheng, Qian Shen, Li Fugen, Li Meng, Lin Tongyu
Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No.55, Section 4, South Renmin Road, Chengdu, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
J Hematol Oncol. 2025 Apr 27;18(1):50. doi: 10.1186/s13045-025-01697-z.
Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL.
A phase Ib clinical trial in PTCL was conducted from July 2022-August 2023 at 15 sites in China. The study employed a dose-escalation phase (300 mg, 400 mg, and 600 mg BID) to determine the recommended phase II dosage (RP2D), followed by a dose expansion phase (300 mg and 400 mg BID). The primary endpoints were safety and the overall response rate (ORR).
Thirty-four patients with various r/r PTCL histology types, a median age of 58 years, and a median of 2 prior systemic therapies were enrolled. Treatment-related adverse events (TRAEs) were observed in 92.1% of the patients, with 20.6% experiencing grade 3 TRAEs. The most common TRAEs included anemia (67.6%), thrombocytopenia (52.9%), leukopenia (44.1%), and diarrhea (38.2%). One patient (2.9%) receiving 600 mg BID experienced dose-limiting toxicity due to grade 4 thrombocytopenia. The dose of 400 mg BID was selected as the RP2D. The ORR was 67.6%, comprising 29.4% complete remission and 38.2% partial remission. As of the data cutoff in September 2024, the median follow-up period was 15.7 months, with a median duration of response of 14.8 months; overall survival had not yet been reached.
The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population.
NCT04390737.
外周T细胞淋巴瘤（PTCL）是一种侵袭性恶性肿瘤，治疗选择有限且预后较差，尤其是对于复发或难治性（r/r）患者。HH2853是一种新型的EZH1/2双重抑制剂，此前已在实体瘤中显示出临床益处。在此，我们报告HH2853治疗r/r PTCL的Ib期试验的安全性和有效性数据。
2022年7月至2023年8月在中国的15个地点进行了一项PTCL的Ib期临床试验。该研究采用剂量递增阶段（300毫克、400毫克和600毫克，每日两次）来确定推荐的II期剂量（RP2D），随后是剂量扩展阶段（300毫克和400毫克，每日两次）。主要终点是安全性和总缓解率（ORR）。
纳入了34例患有各种r/r PTCL组织学类型、中位年龄为58岁且中位接受过2次全身治疗的患者。92.1%的患者观察到治疗相关不良事件（TRAEs），20.6%的患者经历3级TRAEs。最常见的TRAEs包括贫血（67.6%）、血小板减少（52.9%）、白细胞减少（44.1%）和腹泻（38.2%）。一名接受600毫克每日两次治疗的患者（2.9%）因4级血小板减少而出现剂量限制性毒性。选择400毫克每日两次的剂量作为RP2D。ORR为67.6%，包括29.4%的完全缓解和38.2%的部分缓解。截至2024年9月的数据截止时，中位随访期为15.7个月，中位缓解持续时间为14.8个月；总生存期尚未达到。
选择性EZH1/2双重抑制剂HH2853在r/r PTCL患者中显示出可接受且可管理的安全性特征和有前景的疗效，表明其对这一难治性患者群体的治疗潜力。
NCT04390737。
